Document Detail

Relapse to cocaine seeking increases activity-regulated gene expression differentially in the prefrontal cortex of abstinent rats.
MedLine Citation:
PMID:  18311559     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Alterations in the activity of the prefrontal and orbitofrontal cortices of cocaine addicts have been linked with re-exposure to cocaine-associated stimuli. OBJECTIVES: Using an animal model of relapse to cocaine seeking, the present study investigated the expression patterns of four different activity-regulated genes within prefrontal cortical brain regions after 22 h or 15 days of abstinence during context-induced relapse. MATERIALS AND METHODS: Rats self-administered cocaine or received yoked-saline for 2 h/day for 10 days followed by 22 h or 2 weeks of abstinence when they were re-exposed to the self-administration chamber with or without levers available to press for 1 h. Brains were harvested and sections through the prefrontal cortex were processed for in situ hybridization using radioactive oligonucleotide probes encoding c-fos, zif/268, arc, and bdnf. RESULTS: Re-exposure to the chamber in which rats previously self-administered cocaine but not saline, regardless of lever availability, increased the expression of all genes in the medial prefrontal and orbitofrontal cortices at both time points with one exception: bdnf mRNA was significantly increased in the medial prefrontal cortex at 22 h only if levers previously associated with cocaine delivery were available to press. Furthermore, re-exposure of rats to the chambers in which they received yoked saline enhanced both zif/268 and arc expression selectively in the orbitofrontal cortex after 15 days of abstinence. CONCLUSIONS: These results support convergent evidence that cocaine-induced changes in the prefrontal cortex are important in regulating drug seeking following abstinence and may provide additional insight into the molecular mechanisms involved in these processes.
M C Hearing; S W Miller; R E See; J F McGinty
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-03-03
Journal Detail:
Title:  Psychopharmacology     Volume:  198     ISSN:  0033-3158     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-01     Completed Date:  2008-11-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  77-91     Citation Subset:  IM    
Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue BSB 403, Charleston, SC 29245, USA.
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MeSH Terms
Brain-Derived Neurotrophic Factor / biosynthesis,  genetics
Cocaine-Related Disorders / psychology*
Conditioning, Operant / drug effects
Cytoskeletal Proteins / biosynthesis
Early Growth Response Protein 1 / drug effects,  genetics
Gene Expression Regulation / drug effects,  physiology*
Genes, fos / drug effects
Image Processing, Computer-Assisted
In Situ Hybridization
Motor Activity / physiology*
Nerve Tissue Proteins / biosynthesis
Prefrontal Cortex / drug effects,  metabolism*
Rats, Sprague-Dawley
Self Administration
Substance Withdrawal Syndrome / metabolism*,  psychology*
Grant Support
Reg. No./Substance:
0/Brain-Derived Neurotrophic Factor; 0/Cytoskeletal Proteins; 0/Early Growth Response Protein 1; 0/Egr1 protein, rat; 0/Nerve Tissue Proteins; 0/activity regulated cytoskeletal-associated protein

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